Comprehensive analysis of genes involved in the regulation of subcellular localization of drug transporters

• Project/Area Number: 19390017
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: The University of Tokyo
• Principal Investigator: KONTANI Kenji The University of Tokyo, 大学院・薬学系研究科, 准教授 (30302615)
• Co-Investigator(Kenkyū-buntansha): KATADA Toshiaki 東京大学, 大学院・薬学系研究科, 教授 (10088859) ; FUKUYAMA Masamitsu 東京大学, 大学院・薬学系研究科, 助教 (20422389) ; KOBAYASHI Tetsuo 東京大学, 大学院・薬学系研究科, 助教 (80433994)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000); Fiscal Year 2008: ¥9,100,000 (Direct Cost: ¥7,000,000、Indirect Cost: ¥2,100,000); Fiscal Year 2007: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
• Keywords: 薬物トランスポーター / 上皮細胞 / 線虫 / 細胞内輸送 / スクリーニング / RNAi / 細胞極性 / メンブラントラフィック

Research Abstract

薬物トランスポーターPGP-1のアピカル膜への局在制御に関与する因子群を明らかにする目的で、PGP-1-GFPを発現するトランスジェニック線虫を作成し、それを用いてRNAi及び突然変異誘発法による遺伝学的スクリーニングを行った。その結果、微小管に沿って小胞を輸送するモータータンパク質であるダイニン/ダイナクチン複合体の構成因子や膜融合に関与するSNAP29などがPGP-1のアピカル膜への局在制御に関与していることが明らかとなった。

Research Products

• [Journal Article] Blockage by SP600125 of Fcepsilon receptor-induced degranulation and cytokine gene expression in mast cells is mediated through inhibition of phosphatidylinositol 3-kinase signalling pathway. (2009)
  • Author(s): Tanemura S, Momose H, Shimizu N, Kitagawa D, Seo J, Yamasaki T, Nakagawa K, Kajiho H, Penninger JM, Katada T, Nishina H
  • Journal Title: J Biochem. 145(Cover of the issue) Pages: 345-354
  • Peer Reviewed
• [Journal Article] Hematopoiesis-dependent expression of CD44 in murine hepatic progenitor cells. (2009)
  • Author(s): Ohata S, Nawa M, Kasama T, Yamasaki T, Sawanobori K, Hata S, Nakamura T, Asaoka Y, Watanabe T, Okamoto H, Hara T, Terai S, Sakaida I, Katada T, Nishina H
  • Journal Title: Biochem Biophys Res Commun. 379 Pages: 817-823
  • Peer Reviewed
• [Journal Article] Biochemical characterization of missense mutations in the Arf/Arl-family small GTPase Arl6 causing Bardet-Biedl syndrome. (2009)
  • Author(s): Kobayashi T, Hori Y, Ueda N, Kajiho H, Muraoka S, Shima F, Kataoka T, Kontani K, Katada T
  • Journal Title: Biochem Biophys Res Commun. 381 Pages: 439-442
  • Peer Reviewed
• [Journal Article] Arf-like protein 13B. (2009)
  • Author(s): Kontani K, Hori Y, Katada T
  • Journal Title: Nature Molecule Pages (Published online)
  • Peer Reviewed
• [Journal Article] Pax6-5a promotes neuronal differentiation of murine embryonic stem cells. (2009)
  • Author(s): Shimizu N, Watanabe H, Kubota J, Wu J, Saito R, Yokoi T, Era T, Iwatsubo T, Watanabe T, Nishina S, Azuma N, Katada T, Nishina H
  • Journal Title: Biol. Pharm. Bull. 32(6)(Cover of the issue) Pages: 999-1003
  • NAID: 130000117177
  • Peer Reviewed
• [Journal Article] CrxOS maintains the self-renewal capacity of murine embryonic stem cells. (2009)
  • Author(s): Saito R, Yamasaki T, Nagai Y, Wu J, Kajiho H, Yokoi T, Noda E, Nishina S, Niwa H, Azuma N, Katada T, Nishina H
  • Journal Title: Biochem. Biophys. Res. Commun. 390(4) Pages: 1129-1135
  • Peer Reviewed
• [Journal Article] Retinoic acid signaling positively regulates liver specification by inducing wnt2bb gene expression in medaka. (2009)
  • Author(s): Negishi T, Nagai Y, Asaoka Y, Ohno M, Namae M, Mitani H, Sasaki T, Shimizu N, Terai S, Sakaida I, Kondoh H, Katada T, Furutani-Seiki M, Nishina H
  • Journal Title: Hepatology 51(3) Pages: 1037-1045
  • Peer Reviewed
• [Journal Article] Antagonistic control of cell fates by JNK and p38-MAPK signaling. (2008)
  • Author(s): Wada T, Stepniak E, Hui L, Leibbrandt A, Katada T, Nishina H, Wagner EF, Penninger JM
  • Journal Title: Cell Death Differ. 15 Pages: 89-93
  • Peer Reviewed
• [Journal Article] Alteration of enzymatic properties of cell-surface antigen CD38 by agonistic anti-CD38 antibodies that prolong B cell survival and induce activation. (2008)
  • Author(s): Hara-Yokoyama M, Kimura T, Kaku H, Wakiyama M, Kaitsu Y, Inoue M, Kusano S, Shirouzu M, Yokoyama S, Katada T, Hirabayashi Y, Takatsu K, Yanagishita M
  • Journal Title: Int. Immunopharmacol. 8 Pages: 59-70
  • Peer Reviewed
• [Journal Article] Novel antibody to human BASP1 labels apoptotic cells post-caspase activation. (2008)
  • Author(s): Ohsawa S, Watanabe T, Katada T, Nishina H, Miura M
  • Journal Title: Biochem. Biophys. Res. Commun. 371 Pages: 639-643
  • Peer Reviewed
• [Journal Article] Tyr-phosphorylation signals translocate RIN3, the small GTPase Rab5-GEF, to early endocytic vesicles. (2008)
  • Author(s): Yoshikawa M, Kajiho H, Sakurai K, Minoda T, Nakagawa S, Kontani K, Katada T
  • Journal Title: Biochem. Biophys. Res. Commun. 372 Pages: 168-172
  • Peer Reviewed
• [Journal Article] Domain architecture of the atypical Arf-family GTPase Arl13b involved in cilia formation. (2008)
  • Author(s): Hori Y, Kobayashi T, Kikko Y, Kontani K, Katada T
  • Journal Title: Biochem. Biophys. Res. Commun. 373 Pages: 119-124
  • Peer Reviewed
• [Journal Article] Upf1 potentially serves as a RING-related E3 ubiquitin ligase via its association with Upf3 in yeast. (2008)
  • Author(s): Takahashi S, Araki Y, Ohya Y, Sakuno T, Hoshino S, Kontani K, Nishina H, Katada T
  • Journal Title: RNA 14 Pages: 1950-1958
  • Peer Reviewed
• [Journal Article] Upf1 potentially serves as a RING-related E3 ubiquitin ligase via its association with Upf3 in yeast (2008)
  • Author(s): Takahashi, S., et al.
  • Journal Title: RNA 14 Pages: 1950-1958
  • Peer Reviewed
• [Journal Article] Tyr-phosphorylation signals translocate RIN3, the small GTPase Rab5-GEF, to early endocvtic vesicles (2008)
  • Author(s): Yoshikawa, M., et al.
  • Journal Title: Biochem.Biophys.Res.Commun. 372 Pages: 168-172
  • Peer Reviewed
• [Journal Article] Domain architecture of the atypical Arf-family GTPase Arll3b in volved in cilia formation (2008)
  • Author(s): Hori, Y., et al.
  • Journal Title: Biochem.Biophys.Res.Commun. 373 Pages: 119-124
  • Peer Reviewed
• [Journal Article] Caf1 regulates translocation of ribonucleotide reductase by releasing nucleoplasmic Spd1-Suc22 assembly. (2007)
  • Author(s): Takahashi S, Kontani K, Araki Y, Katada T
  • Journal Title: Nucleic Acid Res. 35 Pages: 1187-1197
  • Peer Reviewed
• [Journal Article] Role of activation of PIP5Kgamma661 by AP-2 complex in synaptic vesicle endocytosis. (2007)
  • Author(s): Nakano-Kobayashi A, Yamazaki M, Unoki T, Hongu T, Murata C, Taguchi R, Katada T, Frohman MA, Yokozeki T, Kanaho Y
  • Journal Title: EMBO J. 26 Pages: 1105-1116
  • Peer Reviewed
• [Journal Article] GTP binding is essential to the protein kinase activity of LRRK2, a causative gene product for familial Parkinson's disease. (2007)
  • Author(s): Ito G, Okai T, Fujino G, Takeda K, Ichijo H, Katada T, Iwatsubo T
  • Journal Title: Biochemistry 46 Pages: 1380-1388
  • Peer Reviewed
• [Journal Article] Characterization of Rab45/RASEF containing EF-hand domain and a coiled-coil motif as a self-associating GTPase. (2007)
  • Author(s): Shintani M, Tada M, Kobayashi T, Kajiho H, Kontani K, Katada T
  • Journal Title: Biochem Biophys Res Commun. 357 Pages: 661-667
  • Peer Reviewed
• [Journal Article] Activation of the c-Jun N-terminal kinase pathway by MST1 is essential and sufficient for the induction of chromatin condensation during apoptosis. (2007)
  • Author(s): Ura S, Nishina H, Gotoh Y, Katada T
  • Journal Title: Mol Cell Biol. 27 Pages: 5514-5522
  • Peer Reviewed
• [Journal Article] Mechanism of mRNA deadenylation: evidence for a molecular interplay between translation termination factor eRF3 and mRNA deadenylases. (2007)
  • Author(s): Funakoshi Y, Doi Y, Hosoda N, Uchida N, Osawa M, Shimada I, Tsujimoto M, Suzuki T, Katada T, Hoshino S
  • Journal Title: Genes Dev. 23 Pages: 3135-3148
  • Peer Reviewed
• [Journal Article] IFT-81 and IFT-74 are required for intraflagellar transport in C. elegans. (2007)
  • Author(s): Kobayashi T, Gengyo-Ando K, Ishihara T, Katsura I, Mitani S
  • Journal Title: Genes Cells 12 Pages: 593-602
  • Peer Reviewed
• [Journal Article] The SM protein VPS-45 is required for RAB-5-dependent endocytic transport in Caenorhabditis elegans. (2007)
  • Author(s): Gengyo-Ando K, Kuroyanagi H, Kobayashi T, Murate H, Fujimoto K, Okabe S, Mitani S
  • Journal Title: EMBO Rep. 8 Pages: 152-157
  • Peer Reviewed
• [Journal Article] C. elegans mitochondrial factor WAH-1 promotes phosphatidylserine externalization in apoptotic cells Through phospholipid scramblase SCRM-1. (2007)
  • Author(s): Wang X, Wang J, Gengyo-Ando K, Gu L, Sun C-L, Yang C, Shi Y, Kobayashi T, Shi Y, Mitani S, Xie X-S, Xue D
  • Journal Title: Nat. Cell Biol. 9 Pages: 541-549
  • Peer Reviewed
• [Journal Article] Mechanism of mRNA deadenylation : evidence for a molecular interplay between translation termination factor eRF3 and mRNA deadenylases (2007)
  • Author(s): Funakoshi, Y., et al.
  • Journal Title: Genes Dev. 21 Pages: 3135-3148
  • Peer Reviewed
• [Journal Article] Caf1 regulates translocation of ribonucleotide reductase by releasing nucleoplasmic Spd1-Suc22 assembly (2007)
  • Author(s): Takahashi, S., et al.
  • Journal Title: Nucleic Acid Res. 35 Pages: 1187-1197
  • Peer Reviewed
• [Journal Article] Characterization of Rab45/RASEF containing EF-hand domain and a coiled-coil motif as a self-associating GTPase (2007)
  • Author(s): Shintani, M., et al.
  • Journal Title: Biochem. Biophys. Res. Commun. 357 Pages: 661-667
  • Peer Reviewed
• [Journal Article] Activation of the JNK pathway by MST1 is essential and sufficient for the induction of chromatin condensation during apoptosis (2007)
  • Author(s): Ura, S., et al.
  • Journal Title: Mol. Cell Biol. 27 Pages: 5514-5522
  • Peer Reviewed
• [Journal Article] Role of activation of PIP5Kg661 by AP-2 complex in synaptic vesicle endocytosis (2007)
  • Author(s): Nakano-Kobayashi, A., et al.
  • Journal Title: EMBO J. 26 Pages: 1105-1116
  • Peer Reviewed
• [Presentation] The insulin/IGF signaling and Rag-mediated pathways couple nutrients and stem cell quiescence in C. elegans (2009)
  • Author(s): 福山征光, 他
  • Organizer: 第32回日本分子生物学会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-12
• [Presentation] ユニークな一次構造を有するRabファミリーG蛋白質Rab45の機能解析 (2009)
  • Author(s): 新谷真未, 他
  • Organizer: 第32回日本分子生物学会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-11
• [Presentation] The Arf-like GTPase ARL-8 is required for lysosome biogenesis in C. elegans (2009)
  • Author(s): 中江郁青, 他
  • Organizer: 第32回日本分子生物学会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-11
• [Presentation] リソソームの成熟過程に介在する新奇低分子量Gタンパク質Arl8:Gタンパク質が果たす役割の拡大に向けて (2009)
  • Author(s): 堅田利明
  • Organizer: 高崎健康福祉大学・薬学部
  • Place of Presentation: 高崎
  • Year and Date: 2009-11-27
• [Presentation] アミノ酸シグナルにおけるRagの機能解析 (2009)
  • Author(s): 福山征光, 他
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-24
• [Presentation] 後期エンドソームとリソソームの融合・再形成過程に介在する低分子量G蛋白質Arl8 (2009)
  • Author(s): 堅田利明, 他
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-23
• [Presentation] 体外栄養源による配偶子幹細胞の発生進行制御機構の解明 (2009)
  • Author(s): 福山征光
  • Organizer: 文部科学省科学研究費補助金新学術領域研究「配偶子幹細胞制御機構」領域会議
  • Place of Presentation: 葉山(口頭発表)
  • Year and Date: 2009-10-14
• [Presentation] リソソームにおける低分子G蛋白質Arl8の機能解析 (2009)
  • Author(s): 紺谷圏二, 中江郁青, 堅田利明
  • Organizer: 文部科学省特定領域研究「細胞情報ネットワークを統合するG蛋白質シグナル研究の新展開」班会議
  • Place of Presentation: 南房総・富浦
  • Year and Date: 2009-09-11
• [Presentation] ユニークな一次構造を有するG蛋白質Rab45の生理機能の解析 (2009)
  • Author(s): 新谷真未, 他
  • Organizer: 文部科学省特定領域研究「細胞情報ネットワークを統合するG蛋白質シグナル研究の新展開」班会議
  • Place of Presentation: 南房総・富浦
  • Year and Date: 2009-09-10
• [Presentation] 繊毛形成に関与するG蛋白質Arl13bの機能解析 (2009)
  • Author(s): 堀裕次, 他
  • Organizer: 文部科学省特定領域研究「細胞情報ネットワークを統合するG蛋白質シグナル研究の新展開」班会議
  • Place of Presentation: 南房総・富浦
  • Year and Date: 2009-09-10
• [Presentation] The Arf-like GTPase ARL-8 is required for lysosome biogenesis in C. elegans (2009)
  • Author(s): Nakae I, 他
  • Organizer: 17th International C. elegans Meeting
  • Place of Presentation: Los Angeles, CA, USA
  • Year and Date: 2009-06-27
• [Presentation] Distinct control of survival, and somatic and germline development during L1 diapause by the insulin/IGF signaling and AMPK pathway (2009)
  • Author(s): Fukuyama M, 他
  • Organizer: 17th International C. elegans Meeting
  • Place of Presentation: Los Angeles, CA, USA
  • Year and Date: 2009-06-26
• [Presentation] 繊毛に局在するG蛋白質Arl13bの性状解析 (2009)
  • Author(s): 堀裕次, 他
  • Organizer: 第61回日本細胞生物学会大会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-06-04
• [Presentation] リソソーム酵素の成熟過程における低分子量G蛋白質Arl8の機能解析 (2009)
  • Author(s): 菊香順史, 他
  • Organizer: 文部科学省特定領域研究「生体膜トランスポートソームの分子構築と生理機能」「細胞情報ネットワークを統合するG蛋白質シグナル研究の新展開」合同若手ワークショップ
  • Place of Presentation: 神戸
  • Year and Date: 2009-01-30
• [Presentation] ユニークな一次構造を有するG蛋白質Rab45の生理機能の解明 (2009)
  • Author(s): 新谷真未, 他
  • Organizer: 文部科学省特定領域研究「生体膜トランスポートソームの分子構築と生理機能」「細胞情報ネットワークを統合するG蛋白質シグナル研究の新展開」合同若手ワークショップ
  • Place of Presentation: 神戸
  • Year and Date: 2009-01-29
• [Presentation] 低分子量G蛋白質Arl8の活性制御機構の解明 (2008)
  • Author(s): 菊香順史, 他
  • Organizer: 第31回日本分子生物学会・第81回日本生化学会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] 低分子量G蛋白質Arl8の活性制御機構の解明 (2008)
  • Author(s): 菊香順史, 他
  • Organizer: 第31回日本分子生物学会・第81回日本生化学会合同大会BMB2008
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] The Arf-like GTPase Arl8 is required for lysosome biogenesis in C. elegans. (2008)
  • Author(s): Katada T, 他
  • Organizer: IUPS 2009: PSJ Symposium, VI-5; Recent progress on G-protein signalings
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2008-07-28
• [Presentation] バルデー・ビードル症候群に関わる低分子量Gタンパク質Arl6変異体の性状解析 (2008)
  • Author(s): 堀裕次, 他
  • Organizer: 第60回日本細胞生物学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2008-06-30
• [Presentation] Functional analysis of the Arf-like small GTPase Arl8 in lysosomes (2007)
  • Author(s): 紺谷圏二, 他
  • Organizer: 第30回日本分子生物学会・第80回日本生化学会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-13
• [Presentation] Functional analysis of the Arf-like small GTPase Arl8 in lysosomes (2007)
  • Author(s): 紺谷圏二
  • Organizer: 第30回日本分子生物学会・第80回日本生化学会 合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-13
• [Presentation] 線虫を用いた低分子G蛋白質Arl8の機能解析 (2007)
  • Author(s): 紺谷圏二, 他
  • Organizer: 文部科学省特定領域研究「細胞情報ネットワークを統合するG蛋白質シグナル研究の新展開」班会議
  • Place of Presentation: 東京
  • Year and Date: 2007-07-26
• [Remarks]
  • URL: http://www.f.u-tokyo.ac.jp/~seiri